title: Topically active carbonic anhydrase inhibitors. 3. Benzofuran- and indole-2-sulfonamides.
abstract: Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compounds for clinical use was precluded by the observation that they cause dermal sensitization in guinea pigs. A correlation between electrophilicity, as assessed by in vitro reactivity with reduced glutathione, and dermal sensitization potential was further documented.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: S L
authors.initials: SL
authors.lastname: Graham
authors.forename: J M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: P
authors.initials: P
authors.lastname: Gautheron
authors.forename: S R
authors.initials: SR
authors.lastname: Michelson
authors.forename: T H
authors.initials: TH
authors.lastname: Scholz
authors.forename: H
authors.initials: H
authors.lastname: Schwam
authors.forename: K L
authors.initials: KL
authors.lastname: Shepard
authors.forename: A M
authors.initials: AM
authors.lastname: Smith
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Sondey
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001572:Benzofurans / Q000009:adverse effects; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D004342:Drug Hypersensitivity; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000009:adverse effects; D007700:Kinetics; D009798:Ocular Hypertension / Q000188:drug therapy; D010084:Oxidation-Reduction; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides
chemical_list: D001572:Benzofurans; D002257:Carbonic Anhydrase Inhibitors; D007211:Indoles; D013449:Sulfonamides; D005978:Glutathione